Conformational Modeling of Elastin Tetrapeptide Boc-Gly-Leu-Gly-Gly-NMe by Molecular Dynamics Simulations with Improvements to the Thermalization Procedure

Abstract

Molecular Dynamics Simulations (MD) at Constant-Temperature or Constant-total Energy for the conformational Global-Minimum (GM) of elastin tetrapeptide Boc-Gly-Leu-Gly-Gly-NMe have been performed. The thermalization problem concerning the initial state of Constant-Temperature MD has been solved developing two effective strategies. In the first one, the run starts from the room-temperature state reached by Molecular Dynamics Simulated Annealing (SA). In the second one, one starts from the annealed-state at low-temperature and performs a long constant-low-temperature run until the initial conformer is perfectly equilibrated. Then, the low-temperature equilibrated-state is used as initial state for MD at room-temperature. heuristic criteria on order to define the onset of steady-state have been established monitoring the hystories of collective parameters (e.g., the total energy, temperature, end-to-end distance, etc.) and their amplitude fluctuations. Moreover, the equilibrium between the system and the heat bath is verified analyzing the total linear momentum conservation by the time evolution of center mass velocity. The slow drift of total energy during Constant-total Energy MD has been corrected using a loose coupling between the system and the heat bath. Moreover, we have verified that the roto-translational motions do not affect significantly the properties of molecular vibrations. The librations of peptide unit inside the type II beta-turn [Gly1]C = 0 ... HN[Gly4], previously detected, were confirmed. Large -Gly-Gly- chain motions were identified and modeled as fluctuations occurring between the tetratepeptide GM and the saddle-point corresponding to the transition state of the conversion toward the extended-chain conformation. All these peptide motions could contribute to the elasticity mechanism of elastin.

Quantum Molecular Modeling of the Elastinic Tetrapeptide Val-Pro-Gly-Gly

“…As a matter of fact, previous and present experimental results, as well as quantum calculations, do confirm the particular, intrinsic stability of type II ~-turns having the sequence Pro-Gly at the corners. This is at variance with what was found for Gly-Gly sequences (12) suggesting a "conformation freezing" role for Pro residues in elastin. In other words, it is tempting to suggest that, in the context of a very labile global structure of elastin, Pro-containing ~-turns act as somewhat constrained small areas whose structural role would possibly be that of favouring an inversion of direction of the polypeptide chain.…”

“…Synthetic peptides corresponding to these sequences have been studied together with soluble elastins such as a-elastin and tropoelastin, and gave usefull structural information (4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Structural characterization of VGVAPG, an elastin‐derived peptide

“…This observation is fully consistent with the sliding ␤-turn description of Tamburro, describing ␤-turns as dynamical structures that interchange continuously, and constituting one of the sources of the elastin intrinsic entropy. 39,40 The , dihedral angles fluctuations of the Val3 and Ala4 residues that define the turn type on GVAP are plotted in Figure 5A and B. The figure shows that the GVAP turn is originated by a very fast flipping of the Val3 residue (the first central residue of the turn) from the extended region to the ␣-helical one as described by the Val3 dihedral angle value.…”

Effect of glucose on the biomechanical function of arterial elastin

“…Water plays an essential role in the molecular dynamics of elastin by facilitating the motions of the polypeptide chains (Debelle and Tamburro 1999; Villani and Tamburro 1995; Villani et al 2000). The elastin network contains intrafibrillar, extrafibrillar and bulk water (Lillie et al 1996).…”